Runze Zhang,Kexin Liu,Fangran Jia,Tianci Xu,Yongjie Yang
Leuco-malachite green (LMG) and leuco-crystal violet (LCV) are widespread co-pollutants in aquatic products that pose a severe threat to human health. Therefore, it is urgent and challenging to develop rapid multiplex detection of LMG and LCV. Herein, the bispecific aptamer (A5b) for LMG and LCV was characterized. Its dissociation constant (Kd) was 2.03 ± 0.13 μM for LMG and 0.97 ± 0.06 μM for LCV. Then, we used A5b as a sensing probe to develop a label-free colorimetric aptasensor using gold nanoparticles (AuNPs) as an indicator and poly-diallyl dimethylammonium chloride (PDDA) as an aggregation inducer. In the absence of LMG and LCV, PDDA hybridized A5b via electrostatic interaction to form a “duplex” structure, which failed to induce the aggregation of AuNPs. However, in the presence of LMG or LCV, A5b specifically bound to LMG or LCV, releasing PDDA. The free PDDA then induced the aggregation of AuNPs. Consequently, a visible color change from red to blue was observed with increasing LMG/LCV concentration. This sensor exhibited excellent sensitivity and bispecificity, and a limit of detection (LOD) of 77.9 nM for LCV and 123.1 nM for LMG, with a linear concentration range of 1–6 μM for LCV and 1–8 μM for LMG. Additionally, the potential of this sensor for real-world applications was well demonstrated in crucian samples. Overall, this work provided a bispecific affinity probe for LMG and LCV for the first time and reported a label-free colorimetric aptasensor for multiplex detection of LMG and LCV in aquatic products.
A bispecific thermosensitive system was created to deliver drugs and aid T cells in identifying cancer cells for enhancing the tumor-killing effect. Among various nanocarriers, gold nanocages (AuNCs) were selected as the photothermal agents for photothermal therapy (PTT) due to their distinctive hollow and void structures, which make them ideal carriers throughout the therapy. To achieve controlled drug release under near-infrared radiation, lauric acid (LA) was chosen as the “gatekeeper”, responding to a temperature stimulus. Bispecific aptamers with surface modifications were utilized to increase the intracellular drug content while triggering the immune system to eliminate the cancer cells. The homologous targeting ability of AuNCs/LA/ doxorubicin (DOX)/Apt resulted in a high tumor site aggregation. PTT-induced in situ tumor heat elimination and increased tumor cell immunogenicity upon exposure to laser irradiation. Consequently, the smart nano platform not only destroyed the tumor cells through PTT and chemotherapy but also formed a T cell–cancer cell complex at the tumor site, causing the immune cells to precisely identify the tumor and achieve in situ activation of the immune response at the tumor site. The proposed strategy was a classic “cocktail therapy”.
The insufficient activation and impaired effector functions of T cells in the immunosuppressive tumor microenvironment (TME) substantially reduces the immunostimulatory effects of radiotherapy. Herein, a multifunctional nanoradiosensitizer is established by integrating molecularly engineered aptamer precursors into cisplatin-loaded liposomes for enhancing radio-immunotherapy of solid tumors. Exposure to ionizing radiation (IR) following the nanoradiosensitizer treatment would induce pronounced immunogenic death (ICD) of tumor cells through cisplatin-mediated radiosensitization while also trigger the detachment of the aptamer precursors, which further self-assemble into PD-L1/PD-1-bispecific aptamer-based T cell engagers (CA) through the bridging effect of tumor-derived ATP to direct T cell binding onto tumor cells in the post-IR TME in a spatial-temporally programmable manner. The CA-mediated post-IR tumor-T cell engagement could override the immunosuppressive barriers in TME and enhance T cell-mediated recognition and elimination of tumor cells while minimizing systemic toxicities. Overall, this work offers an innovative approach to enhance the radio-immunotherapeutic efficacy in the clinics.
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